Is AGPS p.Ala69= (c.207A>G) pathogenic?

AGPS p.Ala69= (c.207A>G) is classified Benign in AGPS (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). Common (popmax 6.02%, afr) — too common for a highly-penetrant pathogenic allele; Associated with rhizomelic chondrodysplasia punctata type 3.

What condition is associated with AGPS p.Ala69= (c.207A>G)?

AGPS p.Ala69= (c.207A>G) is associated with rhizomelic chondrodysplasia punctata type 3, rhizomelic chondrodysplasia punctata (ClinVar).

How is Rhizomelic chondrodysplasia punctata inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AGPS p.Ala69=

Q: How common is AGPS p.Ala69= (c.207A>G) in the general population?

AGPS p.Ala69= (c.207A>G) is common (popmax 6.02%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.207A>G · rs34744592 · VCV157712

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 6.02%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

rhizomelic chondrodysplasia punctata type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.3, phastCons 1
Overall
CADD	14.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.02% African / African-American · 4,401/73,152 alleles

Filtering AF 5.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.81%

Overall 1.39% 21,547/1,550,126 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.02%	17
South Asian	5.83%	17
Ashkenazi Jewishnot grpmax-eligible	2.85%	35
Middle Eastern	1.69%	59
Remaining individualsnot grpmax-eligible	1.55%	65
European (non-Finnish)	0.843%	119
Admixed American	0.741%	135
Finnishnot grpmax-eligible	0.587%	170
East Asian	0.022%	4,542

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AGPS
Protein: p.Ala69=
Coding: c.207A>G
MANE Select: NM_003659
dbSNP: rs34744592
Type: single nucleotide variant
Location: chr2:177392996 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27
Residue 69: the 'disordered' region

Full AGPS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

rhizomelic chondrodysplasia punctata type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhizomelic chondrodysplasia punctata

For Rhizomelic chondrodysplasia punctata (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

AGPS p.Arg182Ter Pathogenic/Likely pathogenic ★★ same condition
AGPS p.Thr309Ile Likely pathogenic ★★ same condition
AGPS c.1855+6C>A Uncertain significance ★★ same condition
AGPS c.*118A>G Uncertain significance ★★ same condition
AGPS p.Asp28Val Uncertain significance ★★ ⚠ same condition
AGPS p.Pro415Leu Uncertain significance ★★ ⚠ same condition
AGPS p.Thr72Ala Uncertain significance ★★ ⚠ same condition
AGPS c.1233+14T>A Benign/Likely benign ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/agps-p-ala69 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown